Weekly regimen of epirubicin and paclitaxel as second-line chemotherapy in patients with metastatic transitional cell carcinoma of urothelial tract: results of a phase II study

Abstract

Until recently, there was no standard second-line treatment for advanced urothelial carcinoma. Although included in first-line regimens, role of anthracyclines was never investigated as second-line therapy. Single-agent paclitaxel showed modest results in this setting. The purpose of this study was to assess the efficacy and toxicity of concomitant weekly administration of epirubicin plus paclitaxel in patients with metastatic urothelial carcinoma previously treated with platinum-based regimens. Between March 2004 and May 2008, thirty-five consecutive pretreated patients with metastatic transitional cell carcinoma of the urothelial tract were enrolled. Median age was 64 years (range 45-72 years), and median ECOG PS was 1 (range 0-1). Patients received epirubicin 25 mg/m(2) and paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of four cycles was administered. One patient (3%) showed a complete response (CR), nine patients (26%) had partial response, stable disease was observed in eight patients (23%) for a disease control rate (DCR) of 52%. The median time to progression (TTP) was 7.6 months (95% CI 3.2-10.7 months) with a median survival time (MST) of 12.6 months (95% CI 4.6-18.8 months). Toxicity was acceptable and manageable: no cases of febrile neutropenia occurred and only two patients (6%) developed grade 3 neuropathy. This is the first study that evaluated the role of anthracyclines in combination with paclitaxel as second-line chemotherapy in metastatic transitional cell carcinoma of the urothelium. Our findings show the substantial activity of weekly regimen of paclitaxel and epirubicin: due to its manageable profile of toxicity, this schedule could represent an interesting therapeutic option in previously treated patients with advanced urothelial carcinoma.

Paclitaxel plus Doxorubicin Chemotherapy as Second-Line Therapy in Patients with Advanced Urothelial Carcinoma Pretreated with Platinum plus Gemcitabine Chemotherapy

“…In our study, median OS and median TTP were slightly shorter than those reported by Rozzi et al [9] (12.6 and 7.6monthsvs.8.9and3.8months,respectively),butthelevels oftoxicityinourstudywerecomparable.Thelowersurvival rates in our study may be associated with higher rates of extranodal involvement and enrolment of patients with an ECOGperformancestatusof2.Inconclusion,inlightofthis retrospective study, 3-weekly paclitaxel plus doxorubicin could represent an interesting option in patients with urothelial carcinoma of the urinary tract, who have failed to respondtoplatinum-andgemcitabine-basedchemotherapy.…”

“…Toxicities in this study were of a mild and acceptabledegree,whileonly1patientsufferedfromfebrile neutropeniaandonly3patientshadgrade3peripheralneuro-pathy [9].…”

“…Although single-agent paclitaxel exhibited a 42% RR in untreated patients, it had a lower RR of 7% in patients who were refractory to prior chemotherapy [5,6]. In 2 current studies, gemcitabine and paclitaxel have been used in combination as a second-line therapyinpatientswhodidnotrespondtotheM-VACregimen.Inthesestudies,objectiveresponserates(ORRs)of30 and41.5%werereported [7,8].InthefirstphaseIIstudythat evaluatedtheroleofanthracyclinesincombinationwithpaclitaxelasasecond-linetherapy,anORRof29%andmedian timetoprogression(TTP)of7.6monthswerereported.The indicated study revealed a significant benefit in the rates of bothTTPandoverallsurvival(OS)inpatientswithurothelial cancer, who had previously received cisplatin or carboplatin plusgemcitabine [9].Weevaluatedtheefficacyandtoxicityof thepaclitaxelplusdoxorubicinasasecond-linetreatmentin patients with urothelial carcinoma of the urinary tract, who hadfailedtorespondtopriorplatinumplusgemcitabinecombinationtherapy. Kaya/Coskun/Ozkan/Sevinc/Yilmaz/ Gumus/Unal/Ozdemir/Alici/Berk/ Degerli/Oner/Ozturk/Kefeli/Camcı the date of the last follow-up.…”

Improved 5-Factor Prognostic Classification of Patients Receiving Salvage Systemic Therapy for Advanced Urothelial Carcinoma

“…These 10 trials were used to discover the potential role of selected new risk factors because they were already available and had been previously used for other retrospective analyses. Thereafter, 5 other phase II trials of salvage therapy were pooled in the validation dataset 16–20 . All of these trials required previous pathological confirmation of UC and the presence of measurable metastatic disease.…”